Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells

Abstract

Background and Purpose Quercetin is a natural polyphenolic flavonoid that displays anti-diabetic properties in vivo. Its mechanism of action on insulin-secreting beta cells is poorly documented. In this work, we have analysed the effects of quercetin both on insulin secretion and on the intracellular calcium concentration ([Ca 2+ ] i) in beta cells, in the absence of any co-stimulating factor. Experimental Approach Experiments were performed on both INS-1 cell line and rat isolated pancreatic islets. Insulin release was quantified by the homogeneous time-resolved fluorescence method. Variations in [Ca 2+ ] i were measured using the ratiometric fluorescent Ca 2+ indicator Fura-2. Ca 2+ channel currents were recorded with the whole-cell patch-clamp technique. Key Results Quercetin concentration-dependently increased insulin secretion and elevated [Ca 2+ ] i. These effects were not modified by the SERCA inhibitor thapsigargin (1 μmol·L -1), but were nearly abolished by the L-type Ca 2+ channel antagonist nifedipine (1 μmol·L -1). Similar to the L-type Ca 2+ channel agonist Bay K 8644, quercetin enhanced the L-type Ca 2+ current by shifting its voltage-dependent activation towards negative potentials, leading to the increase in [Ca 2+ ] i and insulin secretion. The effects of quercetin were not inhibited in the presence of a maximally active concentration of Bay K 8644 (1 μmol·L -1), with the two drugs having cumulative effects on [Ca 2+ ] i. Conclusions and Implications Taken together, our results show that quercetin stimulates insulin secretion by increasing Ca 2+ influx through an interaction with L-type Ca 2+ channels at a site different from that of Bay K 8644. These data contribute to a better understanding of quercetin's mechanism of action on insulin secretion. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.